Mikyas et al., Journal of Molecular Biology, 344 (2004), with permission from Elsevier

A secret unlocked?
Vault particles may have a role in fighting infections.

Vaulting Ahead on a Cellular Puzzle

Deputy News Editor

Cystic fibrosis researchers may have stumbled on at least a partial solution to a long-running mystery in cell biology: the role of mysterious barrel-shaped particles called vaults. A study reported in Science today suggests that vaults help cells in the lungs clear bacterial infections.

Originally discovered about 3 decades ago, vaults exist in various cells in a wide variety of species, including mice, humans, and slime molds. Their unusual cylindrical shape, formed by 96 copies of a molecule called major vault protein (MVP), harbors short strands of RNA of unknown function. These barrels can break apart at the center, with each half opening and closing like the petals on a flower. That's one reason researchers have long suspected that vaults transport material within cells. Some even predicted the particles sequester chemotherapy drugs, because cancer cells that make extra vaults become resistant to chemotherapy drugs. Yet when researchers created mice lacking MVP, the animals seemed normal, deepening the vault mystery.

Microbiologist Gerald Pier of Brigham and Women's Hospital in Boston, Massachusetts, had never heard of vaults until MVP turned up in his lab. His group is trying to understand why the bacterium Pseudomona aeruginosa so commonly infects the lungs of people with cystic fibrosis. They came across MVP while identifying proteins mobilized in lung epithelial cells exposed to the germ. First in cell studies and then in mice lacking MVP, the researchers showed that the vault protein somehow helps epithelial cells internalize P. aeruginosa, which in turn speeds the clearance of an infection. Compared to normal mice, for example, MVP-less mice were 3 times as likely to die when their lungs were infected with the bacterium. "I think this study has pinned down a function of vaults," says Pier.

Veteran vault researchers are delighted at the new clue. "This work clearly shows an important function of vaults in lung epithelia," says immunologist Rik Scheper of VU University Medical Center in Amsterdam, the Netherlands. But, he adds, this still doesn't explain what the structures are doing in other cell types or in other organs. And vault specialist Leonard Rome of the University of California, Los Angeles, notes that simple creatures such as slime molds have vaults, too, suggesting they have a more fundamental role than fighting bacteria. "I hope this [connection to cystic fibrosis] stimulates more work on vault function," says Rome.

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